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HLA Class I and Gen...
HLA Class I and Genetic Susceptibility to Type 1 Diabetes Results From the Type 1 Diabetes Genetics Consortium
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Noble, Janelle A. (author)
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Valdes, Ana Maria (author)
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Varney, Michael D. (author)
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- Carlson, Joyce (author)
- Lund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,Clinical Chemistry, Malmö,Lund University Research Groups
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Moonsamy, Priscilla (author)
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Fear, Anna Lisa (author)
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Lane, Julie A. (author)
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Lavant, Eva (author)
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Rappner, Rebecca (author)
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Louey, Anthony (author)
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Concannon, Patrick (author)
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Mychaleckyj, Josyf C. (author)
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Erlich, Henry A. (author)
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(creator_code:org_t)
- 2010-08-26
- 2010
- English.
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In: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 59:11, s. 2972-2979
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Abstract
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- OBJECTIVE-We report here genotyping data and type 1 diabetes association analyses for HLA class I loci (A, B, and C) on 1,753 multiplex pedigrees from the Type 1 Diabetes Genetics Consortium (T1DGC), a large international collaborative study. RESEARCH DESIGN AND METHODS-Complete eight-locus HLA genotyping data were generated. Expected patient class I (HLA-A, -B, and -C) allele frequencies were calculated, based on linkage disequilibrium (LD) patterns with observed HLA class II DRB1-DQA1-DQB1 haplotype frequencies. Expected frequencies were compared to observed allele frequencies in patients. RESULTS-Significant type 1 diabetes associations were observed at all class I HLA loci. After accounting for LD with HLA class II, the most significantly type 1 diabetes-associated alleles were B*5701 (odds ratio 0.19; P = 4 x 10(-11)) and B*3906 (10.31; P = 4 X 10(-10)). Other significantly type 1 diabetes-associated alleles included A*2402, A*0201, B*1801, and C*0501 (predisposing) and A*1101, A*3201, A*6601, B*0702, B*4403, B*3502, C*1601, and C*0401 (protective). Some alleles, notably B*3906, appear to modulate the risk of all DRB1-DQA1-DQB1 haplotypes on which they reside, suggesting a class I effect that is independent of class H. Other class I type 1 diabetes associations appear to be specific to individual class H haplotypes. Some apparent associations (e.g., C*1601) could be attributed to strong LD to another class I susceptibility locus (B*4403). CONCLUSIONS-These data indicate that HLA class I alleles, in addition to and independently from HLA class H alleles, are associated with type 1 diabetes. Diabetes 59:2972-2979, 2010
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
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Diabetes
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Noble, Janelle A ...
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Valdes, Ana Mari ...
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Varney, Michael ...
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Carlson, Joyce
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Moonsamy, Prisci ...
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Fear, Anna Lisa
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show more...
-
Lane, Julie A.
-
Lavant, Eva
-
Rappner, Rebecca
-
Louey, Anthony
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Concannon, Patri ...
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Mychaleckyj, Jos ...
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Erlich, Henry A.
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show less...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
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Diabetes
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Lund University